Aggregates of Cyanine Dyes: When Molecular Vibrations and Electrostatic Screening Make the Difference

Aggregates of cyanine dyes are currently investigated as promising materials for advanced electronic and photonic applications. The spectral properties of aggregates of cyanine dyes can be tuned by altering the supramolecular packing, which is affected by the length of the dye, the presence of alkyl chains, or the nature of the counterions. In this work, we present a joint experimental and theoretical study of a family of cyanine dyes forming aggregates of different types according to the length of the polymethinic chain. Linear and nonlinear optical spectra of aggregates are rationalized here in terms of an essential-state model accounting for intermolecular interactions together with the molecular polarizability and vibronic coupling. A strategy is implemented to properly account for screening effects, distinguishing between electrostatic intermolecular interactions relevant to the ground state (mean-field effect) and the interactions relevant to the excited states (excitonic effects). To the best of our knowledge, this is the first attempt to simulate nonlinear spectral properties of aggregates of symmetric dyes accounting for molecular vibrations

Understanding TADF: a joint experimental and theoretical study of DMAC-TRZ

Thermally-activated delayed fluorescence (TADF) is a promising strategy to harvest triplets in OLED towards improved efficiency, but several issues must be addressed to fully exploit its potential, including the nature of involved excited singlet and triplet states and their response to the local environment in order to concurrently optimize the dye inside the matrix. Towards this ambitious aim, we present an extensive spectroscopic study of a typical TADF dye in liquid and glassy solvents. TD-DFT results for the same molecule in gas-phase and under an applied electric field are exploited to build a reliable model for the dye, rigorously validated against experiment. The model, accounting for charge transfer and local singlet and triplet states, spin-orbit coupling, conformational and vibrational degrees of freedom, sets the basis for a sound understanding of the photophysics of TADF dyes in different environments. The charge-transfer nature of the fluorescent state and of the almost degenerate phosphorescent state is unambiguously demonstrated. The concurrent role played by conformational degrees of freedom and the matrix polarizability in governing TADF is addressed

Health risks related to illegal and on-line sale of drugs and food supplements: results of a survey on marketed products in Italy from 2011 to 2013

Objectives. The increasing illegal and on-line market of medicines and food supplements is helping the widespread diffusion of harmful counterfeit and forbidden products among consumers of developed countries. The objectives of this survey were the description of the main frauds recognized by public officers and the detection of illegal or counterfeit drugs and food supplements.Methods. Medicines and food supplements found by Police forces on the illegal market or resulting from seizures made by Italian Customs authorities were visually inspected and analysed to evaluate their quality and the presence of other undeclared substances.Results. The visual inspection and the chemical analysis revealed unsuitable packaging (mostly lacking of adequate information for consumers), absence of the declared active substances and presence of undeclared active substances. Products containing doping agents, illegal substances and active ingredients requiring medical supervision were found.Conclusion. The present work confirmed the health risk associated with assumption of medicines purchased on the Internet and from the illegal supply chain and evidenced a new threat to consumer safety related to the presence of pharmaceutical active ingredients in food supplements claiming to contain only “natural ingredients”.

A computational framework for testing hypotheses of the minimal mechanical requirements for cell aggregation using early annual killifish embryogenesis as a model

Introduction: Deciphering the biological and physical requirements for the outset of multicellularity is limited to few experimental models. The early embryonic development of annual killifish represents an almost unique opportunity to investigate de novo cellular aggregation in a vertebrate model. As an adaptation to seasonal drought, annual killifish employs a unique developmental pattern in which embryogenesis occurs only after undifferentiated embryonic cells have completed epiboly and dispersed in low density on the egg surface. Therefore, the first stage of embryogenesis requires the congregation of embryonic cells at one pole of the egg to form a single aggregate that later gives rise to the embryo proper. This unique process presents an opportunity to dissect the self-organizing principles involved in early organization of embryonic stem cells. Indeed, the physical and biological processes required to form the aggregate of embryonic cells are currently unknown.Methods: Here, we developed an in silico, agent-based biophysical model that allows testing how cell-specific and environmental properties could determine the aggregation dynamics of early Killifish embryogenesis. In a forward engineering approach, we then proceeded to test two hypotheses for cell aggregation (cell-autonomous and a simple taxis model) as a proof of concept of modeling feasibility. In a first approach (cell autonomous system), we considered how intrinsic biophysical properties of the cells such as motility, polarity, density, and the interplay between cell adhesion and contact inhibition of locomotion drive cell aggregation into self-organized clusters. Second, we included guidance of cell migration through a simple taxis mechanism to resemble the activity of an organizing center found in several developmental models.Results: Our numerical simulations showed that random migration combined with low cell-cell adhesion is sufficient to maintain cells in dispersion and that aggregation can indeed arise spontaneously under a limited set of conditions, but, without environmental guidance, the dynamics and resulting structures do not recapitulate in vivo observations.Discussion: Thus, an environmental guidance cue seems to be required for correct execution of early aggregation in early killifish development. However, the nature of this cue (e.g., chemical or mechanical) can only be determined experimentally. Our model provides a predictive tool that could be used to better characterize the process and, importantly, to design informed experimental strategies

Medicines informal market in Congo, Burundi and Angola: counterfeit and sub-standard antimalarials

BACKGROUND: The presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines. METHODS: In this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality control consisted in the assay of active substance by means of validated liquid chromatographic methods, uniformity of mass determination, disintegration and dissolution tests. Moreover, a general evaluation on label and packaging characteristics was performed. RESULTS: The results obtained on thirty antimalarial tablet samples containing chloroquine, quinine, mefloquine, sulphadoxine and pyrimethamine showed the presence of different kinds of problems: a general problem concerning the packaging (loose tablets, packaging without Producer name, Producer Country and sometimes without expiry date); low content of active substance (in one sample); different, non-declared, active substance (in one sample); sub-standard technological properties and very low dissolution profiles (in about 50% of samples). This last property could affect the bioavailability and bioequivalence in comparison with branded products and could be related to the use of different excipients in formulation or bad storage conditions. CONCLUSION: This paper evidences that the most common quality problem in the analysed samples appears to be the low dissolution profile. Here it is remarked that the presence of the right active substance in the right quantity is not a sufficient condition for a good quality drug. Dissolution test is not less important in a quality control and often evidences in vitro possible differences in therapeutic efficacy among drugs with the same active content. Dissolution profile can be dramatically affected by the choice of excipients in the oral solid formulation and, in many cases, is out of specifications due to the absence of formulation studies by producers of developing countries

Community-developed checklists for publishing images and image analysis

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However for scientists wishing to publish the obtained images and image analyses results, there are to date no unified guidelines. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here we present community-developed checklists for preparing light microscopy images and image analysis for publications. These checklists offer authors, readers, and publishers key recommendations for image formatting and annotation, color selection, data availability, and for reporting image analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby heighten the quality of microscopy data is in publications.Comment: 28 pages, 8 Figures, 3 Supplmentary Figures, Manuscript, Essential recommendations for publication of microscopy image dat

Comparative characterization of Shiga toxin type 2 and subtilase cytotoxin effects on human renal epithelial and endothelial cells grown in monolayer and bilayer conditions

Published: June 23, 2016Postdiarrheal hemolytic uremic syndrome (HUS) affects children under 5 years old and is responsible for the development of acute and chronic renal failure, particularly in Argentina. This pathology is a complication of Shiga toxin (Stx)-producing Escherichia coli infection and renal damage is attributed to Stx types 1 and 2 (Stx1, Stx2) produced by Escherichia coli O157:H7 and many other STEC serotypes. It has been reported the production of Subtilase cytotoxin (SubAB) by non-O157 STEC isolated from cases of childhood diarrhea. Therefore, it is proposed that SubAB may contribute to HUS pathogenesis. The human kidney is the most affected organ because very Stx-sensitive cells express high amounts of biologically active receptor. In this study, we investigated the effects of Stx2 and SubAB on primary cultures of human glomerular endothelial cells (HGEC) and on a human tubular epithelial cell line (HK-2) in monoculture and coculture conditions. We have established the coculture as a human renal proximal tubule model to study water absorption and cytotoxicity in the presence of Stx2 and SubAB. We obtained and characterized cocultures of HGEC and HK-2. Under basal conditions, HGEC monolayers exhibited the lowest electrical resistance (TEER) and the highest water permeability, while the HGEC/HK-2 bilayers showed the highest TEER and the lowest water permeability. In addition, at times as short as 20-30 minutes, Stx2 and SubAB caused the inhibition of water absorption across HK-2 and HGEC monolayers and this effect was not related to a decrease in cell viability. However, toxins did not have inhibitory effects on water movement across HGEC/HK-2 bilayers. After 72 h, Stx2 inhibited the cell viability of HGEC and HK-2 monolayers, but these effects were attenuated in HGEC/HK-2 bilayers. On the other hand, SubAB cytotoxicity shows a tendency to be attenuated by the bilayers. Our data provide evidence about the different effects of these toxins on the bilayers respect to the monolayers. This in vitro model of communication between human renal microvascular endothelial cells and human proximal tubular epithelial cells is a representative model of the human proximal tubule to study the effects of Stx2 and SubAB related to the development of HUS.Romina S. Álvarez, Flavia Sacerdoti, Carolina Jancic, Adrienne W. Paton, James C. Paton, Cristina Ibarra, María M. Amara

Circular dichroism of molecular aggregates: A tutorial

In this tutorial, we guide the reader through two alternative approaches to the calculation of circular dichroism (CD) spectra of chiral supramolecular assemblies of non-chiral chromophores. The two seemingly different approaches rely on the same basic approximations and are therefore expected to lead to similar results. For a dimer, we obtain explicit analytic expressions for the CD responses in the two approaches and demonstrate the perfect equivalence of the two methods. Numerical results for larger systems further validate this result. We hope that this tutorial will help young students and scientists entering the field to approach the fascinating topic of supramolecular chirality

Integrating Microfabrication into Biological Investigations: the Benefits of Interdisciplinarity

The advent of micro and nanotechnologies, such as microfabrication, have impacted scientific research and contributed to meaningful real-world applications, to a degree seen during historic technological revolutions. Some key areas benefitting from the invention and advancement of microfabrication platforms are those of biological and biomedical sciences. Modern therapeutic approaches, involving point-of-care, precision or personalized medicine, are transitioning from the experimental phase to becoming the standard of care. At the same time, biological research benefits from the contribution of microfluidics at every level from single cell to tissue engineering and organoids studies. The aim of this commentary is to describe, through proven examples, the interdisciplinary process used to develop novel biological technologies and to emphasize the role of technical knowledge in empowering researchers who are specialized in a niche area to look beyond and innovate